The present invention is generally related to medical devices, systems, and methods. In exemplary embodiments, the invention provides catheter-based treatment for body tissues, which may further include treatment for luminal tissues, particularly for vascular stenosis and/or for delivery of energy proximate to a luminal wall. The methods, systems, and structures of the invention allow controlled delivery of tissue treatment energy, tissue remodeling and/or removal, often using both electrical diagnostic and/or control signals and electrosurgical energy.
Physicians use catheters to gain access to and repair interior tissues of the body, particularly within the lumens of the body such as blood vessels. A variety of means are known in the art for providing localized therapeutic effects in the area surrounding the target location. For example, balloon angioplasty, atheterctomy, laser, cryogenic ablation, stents, and other catheter-based treatments of the like often are used to open arteries that have been narrowed due to disease.
Balloon angioplasty is often effective at opening a stenosed blood vessel, but the trauma associated with balloon dilation can impose significant injury, so that the benefits of balloon dilation may be limited in time. Stents are commonly used to extend the beneficial opening of the blood vessel.
Stenting, in conjunction with balloon dilation, is often the preferred treatment for stenotic disease such as atherosclerosis. In stenting, a collapsed metal framework is mounted on a balloon catheter that is introduced into the body. The stent is manipulated into the site of stenosis and expanded in place by the dilation of the underlying balloon. Stenting has gained widespread acceptance, and produces generally acceptable results in many cases. Along with treatment of blood vessels (particularly the coronary arteries), stents can also be used in treating many other tubular obstructions within the body, such as for treatment of reproductive, gastrointestinal, and pulmonary obstructions.
Restenosis occurs when the treated vessel becomes re-blocked following its initial interventional treatment. It usually occurs within six months after the initial procedure. The mechanism of restenosis after balloon angioplasty is a combination of recoil, arterial vessel remodeling, and neointimal hyperplasia. Late lumen loss in stented segments is the result of intimal hyperplasia. Compared with balloon angioplasty alone, where the chance of restenosis may, for example, be estimated to be about 40%, stents have been shown to reduce the chance of restenosis in some cases to about 25%. Therefore, the majority of patients having angioplasty today are treated with stents. Restenosis can occur after the use of stents, and physicians refer to this as in-stent restenosis, which is typically seen three to six months after the stenting procedure. Several approaches have been developed to treat restenosis including ablation, atheroectomy, and drug eluting stents. In addition, work has also been initiated with systemic drug delivery (intravenous or oral) that may also improve procedural success rates. The existing available options for treatment of in-stent restenosis may have limitations such as procedural complexity, constraints caused by the pre-existing implant, limitations in long-term efficacy, extremely high product development costs and protracted regulatory pathways, costly medication regimens, and the challenges of vascular biomechanics in places such as the leg.
In-stent restenosis involves the growth of new tissue within the arterial wall, and may be caused by a biological cascade mechanism of platelets, polymorphonuclear leucocytes, and macrophage aggregation leading to the migration of smooth muscle cells from the media to the intima coupled with smooth muscle cell proliferation at the intimal layer.
The acute onset of in-stent restenosis can begin with relocation of plaque and reorganization of thrombus, in conjunction with an acute inflammatory response to injury of the endothelium that promotes fibrin and platelet deposition. Leucocytes gather in and around the injury caused by balloon dilation and stent implantation. As the biological cascade continues, leucocyte recruitment is further sustained.
As the in-stent restenosis process continues, smooth muscle cells in the medial layer modify and migrate from the medial layer to the intimal layer before further proliferating as neointimal tissue. The volume of stenotic neointimal tissue is increased by smooth muscle cell synthesis of extracellular matrix predominantly comprised of proteoglycans and collagens.
None of the available interventional modalities provides optimal acute results, and long-term results can be poor. This is especially true for diffuse in-stent restenosis lesions, which are common. For example, treatment of a diffuse, long, coronary artery lesion with overlapping bare metal stents has been known to be associated with high rates of restenosis. By way of example, drug eluting stents were thought to be a revolutionary method of significant and sustained suppression of neointimal proliferation in cases of diffuse, long coronary lesions requiring overlapping stents. However, hypersensitivity reactions or cytotoxicity have been shown to be serious problems with stents coated with an antiproliferative drug. Nebeker, et al. have recently published data suggesting that the window of thrombotic risk associated with drug eluting stents extends far beyond that seen with bare metal stents, thus, post-operative anti-platelet therapy may be requisite for drug eluting stent patients (J Am Coll Cardiol (2006), 47: 175-181), the full contents of which are incorporated herein by reference. Furthermore, United States Food and Drug Administration reports and autopsy findings suggest that drug eluting stents may be a cause of systemic and intra-stent hypersensitivity reactions that, in some cases, have been associated with late thrombosis and death. This hypersensitivity or cytotoxicity, possibly induced by the coating comprising the drug carrier, is associated with delayed healing and poor endothelialization (Virmani, et al., Coron Artery Dis (2004), 15: 313-318.), the full contents of which are incorporated herein by reference.
The application of energy to tissue has been shown to promote beneficial therapeutic responses, including for the treatment of tissue in or proximate to a body lumen. For example, thermal energy in controlled dosages may play a role in tissue debulking after thermal therapy by activation of Heat Shock Proteins (HSP's). HSP's are proteins that exist in most living cells (i.e. mammals, plants, and yeast). They often act like “chaperones” to ensure that a cell's normal functional proteins are in the right place at the right time. Their concentrations can increase in response to stress, such as heat, cold or lack of oxygen. Their increased presence can be a signal to the immune system for sick or necrotic cells that require removal, and therefore play a role in tissue debulking after a thermal treatment. Beneficial thermally-induced tissue effects have been disclosed by U.S. patent application Ser. No. 11/975,474 the full disclosure of which is incorporated herein by reference.
The application of energy to tissue proximate to an energy source is not limited to inducing tissue debulking. For example, radiofrequency energy may be used to affect energy conduction in nervous tissue in the fields of electrophysiology and neuromodulation; common examples include cardiac ablation to regulate heartbeat, neuromodulation to affect an expansive array of efferent and afferent nerve activity in physiologic processes such as those of the brain, digestive system, excretory processes, kidney and other organ function, sensory function, and the like.
In the example of thermal treatment of nerve tissue, such treatments may be ablative or non-ablative, wherein ablation causes long-term tissue damage while non-ablative energy may be in the form of stimulation or disruption of nerve conduction. The disruption of nerve conduction may be achieved by means that block or interfere with the transmission of nerve signals, which may for example be accomplished by means that change the nature of nerve tissue properties. The duration and extent of disruption may be tailored to the particular biologic process and may be a function of the energy dosage applied to the target site.
In the example of in-stent restenosis, a controlled application of radiofrequency energy may be used to cause resistive heating, and as a result the hydrogen bonds of the collagen contained in the tissue may be broken. This breaking of bonds may result in a more compliant stenosis that may be made to reshape around a balloon catheter while applying low pressure to the vessel wall (6 or less atmospheres) as opposed to the relatively high pressure (about 10-15 atmosphere) typical of regular balloon angioplasty. Thereby, this may facilitate restenotic tissue compression by the balloon and may result in a larger vessel lumen. In addition, Brasselet et al. have reported that moderate heating represents a promising approach to reduced neointimal hyperplasia by a mechanism involving decreased smooth muscle cell proliferation (Eur Heart J. (2008) 29(3):402-12), the full contents of which are incorporated herein by reference.
In light of the above, it would be advantageous to provide new devices, systems, and methods for diagnosing, characterizing, remodeling, and/or delivering therapeutic energy to tissues, which may further include stenosis of the lumens of the body, and particularly of the blood vessels. Specifically, it would be desirable to provide devices, systems, and methods for treating in-stent restenosis or energy delivery to other tissues proximate to a lumen where the delivery of energy in the form of a controlled dosage provides a means for interrupting biological activity. It would further be desirable to avoid significant cost or complexity while providing structures that could both characterize and remodel or remove target tissues such as plaques or other stenotic materials, nerve tissue, or other tissues such tissues found proximate to a lumen. It is further advantageous to avoid having to resort to the trauma known to be associated with dilation, excessive input of thermal energy to tissue, and the like, which may lead to chronic inflammatory response. It would also be beneficial if diagnosing and treating systems could provide some feedback on the progress of treatment.